Miniaturization of analytical methodology onto microdevices has seen a surge of research interest over the recent decade due to the possibilities of reduced reagent and sample volumes, reduced analysis times, and parallel processing. Another leading advantage of miniaturization is the potential to integrate multiple sample handling steps with analysis steps to achieve integrated, user-friendly, sample-in/answer-out devices—commonly referred to as micro-total-analysis systems (μ-TAS). Many of these emerging μ-TAS can simply be interfaced with a computer for automated, user-friendly applications.
Microfluidic devices are known. For example, U.S. Pat. Nos. 6,130,098 to Handique; 6,919,046 to O'Connor et al.; 6,544,734 to Briscoe et al.; the disclosures of which are incorporated herein by reference, discloses microfluidic devices for use in biological and/or chemical analysis. The system includes a variety of microscale components for processing fluids, including reaction chambers, electrophoresis modules, microchannels, detectors, valves, and mixers. Typically, these elements are microfabricated from silicon, glass, ceramic, polymer, metal, and/or quartz substrates. The various fluid-processing components are linked by microchannels, through which the fluid flows under the control of a fluid propulsion mechanism. If the substrate is formed from silicon, electronic components may be fabricated on the same substrate, allowing sensors and controlling circuitry to be incorporated in the same device. These components can be made using conventional photolithographic techniques, as well as with laser ablation, polymer molding, hot embossing, micromachining, physical/mechanical removal, or similar methods. Multi-component devices can be readily assembled into complex, integrated systems. In most microfluidic research laboratories, photolithography and chemical etching are used in their simplest form to create patterns in a monolithic configuration.
A large breadth of biological and/or chemical analyses is possible with microdevices having multifunction capabilities. The key to creating multifunctional devices with turn-key operation capability will be the integration of processes for total analysis. For example, for genomic analysis, the totally integrated analysis would require that steps such as cell lysis, DNA extraction, DNA purification, and DNA amplification (via PCR) be carried out on-chip prior to electrophoresis on the same microdevice. This promises to provide investigators with a powerful technology that will minimize sample and operator contamination, as well as reduce the potential for concomitant error often induced by sample transfer and the interchange between devices. Other advantages include circumventing the need for large sample volumes (many systems require only nanoliter volumes) and increasing reaction rates (Manz et al. Adv. Chromatogr. 1993, 33:61).
One of the important issues for proper function of a μ-TAS is the control of fluid flow through the microfluidic network of the device. Each compartment or microscale component of the device is connected to another through a microchannel that facilitates the transfer of sample from one location in the microdevice to the next. Moreover, while the various functionalities on the chip are connected by their inherent dependency on one another, they are, nonetheless, independent units carrying out very different chemistries. In fact, the reagents used/contained in any functional domain are often harmful to the processes carried out in other domains. For example, isopropanol and guanidine are critical for the extraction of DNA from cell lysates; however, leakage of either reagents into a PCR domain (one possible pathway in the sample preparation sequence) is fatal to the amplification process (inhibits PCR). As a result, keeping the various domains connected but chemically isolated is a necessity. In more complicated microdevices, this is accomplished with a system of ‘pumps’ and ‘valves’ to control and direct flow from one compartment to the next.
The mechanisms of valve actuation are manifold. Some rely on pneumatic mechanism while others depend upon mechanical pressure or piezoelectric methods. Many systems rely on a flexible, elastomer valve (Unger et al. Science 2000, 288:113; Grover et al. Sens. Actuators B 2003, 89:315) that can be easily manipulated so as to allow on-command distension, while others have utilized pH-sensitive (Yu et al. Phys. Lett. 2001, 78:2589) or thermo-reactive polymers (Harmon et al. Polymer 2003, 44:4547; Yu et al. Anal. Chem. 2003, 75:1958). Olefins (Klintberg et al., Sens. Actuators A 2003, 103:307; Selvaganapathy et al. Sens. Actuators A 2003, 104:275), ferro-fluid (Hatch et al. J. Microelectromechan. Syst. 2001, 10:215), and air bubbles (Song et al. J. Micromech. Microeng. 2001, 11:713; Handique et al. Anal. Chem. 2001, 73:1831; U.S. Pat. No. 6,877,528 to Gilbert et al.) have also been used for valving. Additionally, a number of mechanisms exist for generating flow through the microchannels. The method of Unger et al. starts with all valves in the open position, and then, in a stepwise fashion, each valve closes in series (via pressure actuation) to create a peristaltic pump. Another method by Grover et al. functions similarly to a diaphragm. All valves start in the closed position and flow is accomplished by successive opening (via pneumatic mechanisms) of valves in a determined pattern. Both the Unger et al. and Grover et al. methods use solenoid valves coupled directly into the channel wall and require a separate pump to operate.
Other prior art valves for use in microfluidic devices include U.S. Pat. Nos. 6,901,949 and 6,817,373 to Cox et al.; 6,802,489 to Marr et al.; 6,783,992 to Robotti et al.; 6,748,975 to Hartshorne et al.; 6,698,454 to Sjolander et al.; 6,615,856 to McNeely et al.; 6,581,899 to Williams; 6,561,224 to Cho; 6,431,212 to Hayenga et al.; and 6,382,254 to Yang et al.; the disclosures of which are incorporated herein by reference.
As with most methods used for directing flow through a microchannel network, the prior art valves are not without limitations, which include inefficient flow control, large power requirements, slow response speed, size, portability challenge and restrictions associated with the chemical characteristics of the elastomer as it pertains to the application. Consequently, there is a critical need to develop totally integrated microfluidic devices with valving capabilities that not only meet the needs of the application in a cost-effective manner, but also allow for simple, smooth, and precise control of flow through the microchannel architecture.